Pyridine → N-(4-chloro-5-vinylpyridin-2-yl)acetamide

HRID 1398350Notes

Reaction equation

HRID 1398350 reaction equation
Br[C:2]1[C:3]([Cl:12])=[CH:4][C:5]([NH:8][C:9](=[O:11])[CH3:10])=[N:6][CH:7]=1.N1C=CC=[CH:15][CH:14]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:12][C:3]1[C:2]([CH:14]=[CH2:15])=[CH:7][N:6]=[C:5]([NH:8][C:9](=[O:11])[CH3:10])[CH:4]=1

Participants

8

Reactant 3

HCID 1049PyridineHCID 10340Sodium CarbonateHCID 86695929N-(5-bromo-4-chloropyridin-2-yl)acetamide

Product 1

HCID 86695930N-(4-chloro-5-vinylpyridin-2-yl)acetamideYield 99%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

To a stirred solution of N-(5-bromo-4-chloropyridin-2-yl)acetamide (7 g, 28.1 mmol), 2,4,6-trivinyl-1,3,5,2,4,6-trioxatriborinane complex with pyridine (1:1) (8.78 g, 36.5 mmol), sodium carbonate (5.95 g, 56.1 mmol) solution in 7 mL of water and tetrakis(triphenylphosphine)palladium (0.973 g, 0.842 mmol) in a mixture of Toluene (50 mL) and Ethanol (8 mL), nitrogen gas was bubbled for 5 min. The reaction mixture was heated at 85° C. for 14 hours. After the completion, the reaction was diluted with EtOAc (50 mL), filtered through diatomaceous earth (Celite®). The filtrate was diluted with water and the organic layer was separated, washed with brine solution, dried over sodium sulfate. The organics were concentrated under reduced pressure and residue so obtained was purified by comb flash column 120 g using hexane/ethyl acetate. Product eluted at 30% EtOAc in hexane and required fractions were concentrated to yield N-(4-chloro-5-vinylpyridin-2-yl)acetamide (5.92 g, 27.7 mmol, 99% yield) as yellow solid. LC/MS (ESI) m/e 197.2 [(M+H)+, calcd for C9H10ClN2O 197.04] LC/MS retention time (method A): tR=1.50 min; 1H NMR (400 MHz, DMSO-d6) δ 10.79 (s, 1H), 8.64 (s, 1H), 8.18 (d, J=6.40 Hz, 1H), 6.88 (dd, J=11.20, 17.60 Hz, 1H), 5.99 (dd, J=0.80, 17.60 Hz, 1H), 5.47 (dd, J=0.80, 11.40 Hz, 1H), 2.12 (s, 3H).

Workup

  1. customwas bubbled for 5 min
  2. additionAfter the completion, the reaction was diluted with EtOAc (50 mL)
  3. filtrationfiltered through diatomaceous earth (Celite®)
  4. additionThe filtrate was diluted with water
  5. customthe organic layer was separated
  6. washwashed with brine solution
  7. dry with materialdried over sodium sulfate
  8. concentrationThe organics were concentrated under reduced pressure and residue
  9. customso obtained
  10. customwas purified by comb flash column 120 g
  11. washProduct eluted at 30% EtOAc in hexane
  12. concentrationrequired fractions were concentrated

Sources & evidence

ORD record
ord-ebe78c3a09c34247994bda67a4cba64b
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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